title: Promyogenic function of Integrin/FAK signaling is mediated by Cdo, Cdc42 and MyoD.
abstract: The Integrin-mediated cell adhesion to the extracellular matrix is implicated in the control of proliferation, survival, migration and differentiation of myoblasts. Focal adhesion kinase (FAK) mediates signals from Integrins and plays an essential role in myotube formation. Cdo forms a multiprotein complex that includes other cell adhesion molecules like Cadherins and Boc. Multiple signals emanate from such complexes, including Cdc42 and p38MAPK pathways to activate MyoD. Here we show that C2C12 myoblasts cultured in suspension or on Poly-L-Lysine (PLL), a well known Integrin-independent substratum, failed to express Cdo and MyoD, while the expression of Cadherins and Boc was unchanged. In addition, the activation of Akt and p38MAPK as well as the expression of Cdc42 was affected in these cells. Overexpression of FAK rescued MyoD and Cdo expression as well as myotube formation of C2C12 cells on PLL. Furthermore, reintroduction of Cdo induced enhanced myotube formation on PLL and increased the expression of myogenic markers. Inhibition of ROCK or overexpression of Cdc42-V12 in C2C12 cells upregulated Cdc42 and MyoD expression and rescued defective myoblast differentiation. Taken together, these data indicate that the Integrin/FAK signaling pathway is required for myoblast differentiation by regulating the expression of the promyogenic factors, Cdo, MyoD and Cdc42.
authors.affiliation: Department Molecular Cell Biology, Center for Molecular Medicine, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea.
authors.forename: Ji-Won
authors.initials: JW
authors.lastname: Han
authors.forename: Hye-Jin
authors.initials: HJ
authors.lastname: Lee
authors.forename: Gyu-Un
authors.initials: GU
authors.lastname: Bae
authors.forename: Jong-Sun
authors.initials: JS
authors.lastname: Kang
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D002460:Cell Line; D003470:Culture Media; D004789:Enzyme Activation; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism*; D015870:Gene Expression; D019012:Integrin beta1 / Q000378:metabolism; D016023:Integrins / Q000378:metabolism*; D051379:Mice; D024510:Muscle Development; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D017570:MyoD Protein / Q000235:genetics / Q000378:metabolism*; D032446:Myoblasts / Q000166:cytology / Q000378:metabolism; D011107:Polylysine / Q000378:metabolism; D015398:Signal Transduction; D020764:cdc42 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors
chemical_list: C510744:Cdon protein, mouse; D015815:Cell Adhesion Molecules; D003470:Culture Media; D019012:Integrin beta1; D016023:Integrins; D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein; D011107:Polylysine; D051417:Focal Adhesion Kinase 1; C496051:Ptk2 protein, mouse; D054460:rho-Associated Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D020764:cdc42 GTP-Binding Protein